EORTC QLQ-HCC18 Research Articles

Real-world study of anlotinib monotherapy and combination therapy for unresectable hepatocellular carcinoma.

e16146 Background: Unresectable hepatocellular carcinoma (uHCC) is an aggressive tumor with poor prognosis. Anlotinib is a novel small-molecule tyrosine kinase inhibitor (TKI) that selectively targets VEGFR, FGFR, PDGFR, and c-kit receptors. Clinical trials have confirmed the efficacy and safety of anlotinib monotherapy or anlotinib-based combination therapy for uHCC. However, many patients in clinical practice fail to meet the criteria for these trials. Therefore, this study aimed to investigate the efficacy and safety of anlotinib, as monotherapy or in combination therapy, for uHCC in clinical practice in China. Methods: This multicenter, real-world study enrolled patients with uHCC who had received anlotinib-based therapy, and completed at least one post-treatment efficacy assessment between July 2020 to February 2023. Patients who did not undergo imaging after one cycle of treatment, were lost to follow-up before completing one cycle of treatment, or required systemic chemotherapy or radiotherapy for the primary lesion were excluded from the study. The efficacy assessments were performed based on the RECIST version 1.1. OS, PFS, TTP, DCR and ORR for patients with anlotinib monotherapy (n = 12) and anlotinib-based combination therapy (n = 60) were evaluated. The main statistical analysis was conducted using the Kaplan–Meier method and log-rank test. Subgroup comparisons were performed based on different combinations of anlotinib therapy and the number of treatment lines in patients with uHCC. Occurrence of adverse events (AEs) to evaluate the safety profiles of anlotinib monotherapy or anlotinib-based combination therapy was collected. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire HCC-18 (EORTC QLQ-HCC18) was used to evaluate health-related quality of life (HRQOL). Results: For the anlotinib monotherapy group, the OS, PFS, TTP, DCR and ORR were 14.2 months, 6.9 months, 7.9 months, 16.7%, and 50.0%, respectively. For the anlotinib-based combination therapy group, these values were 15.8 months, 8.6 months, 10.2 months, 25.0%, and 65.0%, respectively. There was no significant difference in OS, PFS, and TTP between the two groups. PFS were significantly decreased in the non-first-line treatment group compared to the first-line treatment group. The incidence of drug-related AEs of any grade was 93.1%, with the most common grade ≥3 treatment-related AEs being lymphopenia and elevated transaminases. The time to deterioration was 14.0 months (95%CI: 8.3–19.8) and 12.2 months (95%CI: 9.8–14.7) in the monotherapy and combination therapy groups. Conclusions: Anlotinib demonstrated satisfactory efficacy and safety as a single agent and in combination with other therapies in the treatment of uHCC, with potential benefit on health-related quality of life.

Patient-reported outcomes (PROs) <65 or ≥ 65 years old (yo) from CARES-310 camrelizumab + rivoceranib vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).

456 Background: CARES-310 (NCT03764293) evaluated the combination of the anti-PD-1 inhibitor, camrelizumab (cam), and the VEGFR-2 tyrosine kinase inhibitor, rivoceranib (rivo), compared to sorafenib (sor) for the treatment of uHCC. Cam + rivo significantly improved OS and PFS compared to sor (OS, 22.1 months [mo] [95% CI 19.1-27.2] vs 15.2 mo [13.0-18.5] HR 0.62 [95% CI 0.49-0.80]; one-sided p<0.0001); PFS, 5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7]; HR 0.52 [95% CI 0.41-0.65]; one-sided p<0.0001). The most common (≥20%) grade ≥3 treatment-related adverse events for cam + rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia syndrome (15.2%) for sor. This analysis evaluated PROs stratified by age: <65 yo (baseline, overall cam + rivo n=191, sor n=210) or ≥65 yo (baseline, overall cam + rivo n=81, sor n=61). Methods: Patients completed EORTC QLQ-C30 and EORTC QLQ-HCC18 at baseline, each visit, and post-last-dose follow-up periods. Endpoints included time to deterioration (TTD) with a ≥10-point decrease from baseline of patient reported QoL, physical functioning, role functioning, and patient-reported symptoms. Results: Mean completion rates across questionnaires were 98.56% and 96.78% for cam + rivo and 98.91% and 98.75% for sor in the <65 and ≥65 yo groups, respectively, from baseline through ≥121 weeks of treatment. In the <65 yo group, cam + rivo vs sor had improved TTD in fatigue measured by EROTC-QLQ-C30. In the ≥65 yo group, cam + rivo had significantly longer median TTD of pain measured by EROTC-QLQ-HCC18 and QLQ-C30, respectively. The median TTD of appetite loss in the ≥65 yo group favored cam + rivo. Median TTD for jaundice was significant for sor in both <65 yo and ≥65 yo group. Median GHS/HRQoL in the ≥65 yo group favored cam + rivo. Conclusions: Cam + rivo was associated with improvement in varied QoL aspects in both patient groups. These PRO results support the clinical benefit and use of cam + rivo in patients with uHCC who have not received prior systemic therapy. Clinical trial information: NCT03764293 . [Table: see text]

Patient-Reported Outcome Measures in Liver and Gastrointestinal Cancer Randomized Controlled Trials.

For many years, outcomes such as mortality and morbidity were the standard for evaluating oncological treatment effectiveness. With the introduction of patient-reported outcome measures (PROMs), the focus shifted from a mere extension of a patient's life or release from disease to the improvement of a multilayered concept of health, decisively affecting life satisfaction. In this study, we deal with the topic of PROMs in liver and gastrointestinal randomized controlled trials. The final database included 43 papers reporting results of randomized controlled trials (RCTs) for liver or gastrointestinal cancer interventions where one of the primary or secondary outcomes was a health-related quality of life measure. The most often used PROM was the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for both liver cancer and gastrointestinal cancer (in 62% of gastrointestinal cancer studies and 57% of liver cancer studies). For the gastrointestinal cancer group, the QLQ-STO22, a cancer-specific extension of the QLQ-C30, was the second most commonly used PROM. In liver cancer, the generic PROM Short Form 36 and the EORTC QLQ-HCC18, a cancer-specific extension of the QLQ-C30, were the second most commonly used PROMs. We found that RCTs often do not include comprehensive quality-of-life measures. When quality of life is part of an RCT, it is often only a secondary outcome. For a holistic view of the patient, a stronger integration and weighting of patient-reported outcomes in RCTs would be desirable.

Health-related quality of life (HRQoL) impact of lenvatinib (len) plus pembrolizumab (pembro) versus len plus placebo (pbo) as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC): Phase 3 LEAP-002 study.

506 Background: In LEAP-002 (NCT03713593), len + pembro achieved a median OS of 21.2 mo vs 19.0 mo with len + pbo with manageable safety in both arms in 1L aHCC, although the significance thresholds for OS and PFS were not met. We present here the results of prespecified exploratory patient (pt)-reported outcomes (PROs). Methods: 794 pts were randomized. PROs were assessed by EORTC QLQ-C30, EuroQol-5D5L (EQ5D-5L), and EORTC QLQ-HCC18 questionnaires. Analysis population for HRQoL endpoints included pts who received ≥1 dose of study Tx and completed ≥1 HRQoL assessment. Least squares mean (LSM) score changes from baseline (BL) to wk 27 were compared using a constrained longitudinal data analysis model (covariates: Tx, time, Tx by time interaction, and stratification factors). Kaplan-Meier method was used to estimate time to deterioration (TTD, time to 1st onset of ≥10 [out of 100] deterioration from BL in a given scale or subscale/confirmed by a 2nd adjacent ≥10 deterioration from BL) for EORTC QLQ-C30 global health status (GHS)/QoL, physical functioning (PF), and EORTC QLQ-HCC18 abdominal swelling, pain and fatigue, as reported by pts. Stratified Cox proportional hazards model was used to assess the magnitude of the Tx difference (HR) between arms in TTD. Results: Compliance with PRO assessments was >91% from BL until wk 27 in both arms. From BL to wk 27, LSM changes in GHS/QoL, PF, role functioning (RF), QLQ-HCC18 functional/domain scores and EQ5D-5L VAS were generally similar between the two arms (Table). Treatment with len + pembro delayed deterioration of patient-reported quality of life vs len + pbo (median TTD, 11.5 vs 4.3 mo; HR, 0.80; 95% CI, 0.65-0.98). LSM score difference (95% CI) was 0.5 (-2.5, 3.4) for GHS/QoL, -1.7 (-4.5, 1.1) for PF, -1.0 (-4.9, 2.9) for RF, 1.0 (-2.2, 4.3) for abdominal swelling, 2.0 (-1.2, 5.2) for fatigue, 2.0 (-1.0, 5.0) for pain, and 0.6 (-2.0, 3.2) for EQ5D-5L VAS. Median TTD in QLQ-C30 PF (5.7 vs 9.1 mo; HR, 1.14; 95% CI, 0.93-1.41) and QLQ-HCC18 abdominal swelling (NR vs NR; HR, 1.19; 95% CI, 0.89-1.60) /fatigue (2.9 vs 2.8 mo; HR, 0.98; 95% CI, 0.81-1.19)/pain (9.6 vs 7.9 mo; HR, 0.93; 95% CI, 0.75-1.16) was similar between the arms. Conclusions: Len + pembro generally preserved HRQoL vs len + pbo in 1L for aHCC. Combined with efficacy and safety results from LEAP-002, these findings support continued development of len + pembro in HCC. Clinical trial information: NCT03713593 . [Table: see text]

Psychometric validation of the EORTC QLQ-HCC18 in patients with previously treated unresectable hepatocellular carcinoma

To demonstrate the measurement properties of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (EORTC QLQ-HCC18) within a previously treated, unresectable hepatocellular carcinoma (HCC) clinical trial population that was distinct from the published QLQ-HCC18 validation population. Analyses were conducted using data from BGB-A317-208, an open label, international, clinical trial assessing efficacy and safety of the monoclonal antibody tislelizumab in adult HCC patients. The EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and QLQ-HCC18 instruments were assessed at baseline and weeks 3 and 9 follow-up visits. Per US Food and Drug Administration guidance, psychometric validation of the QLQ-HCC18 included reliability (internal consistency and test–retest), construct validity (convergent and discriminant validity and known-groups validity), ability to detect change, and meaningful within-patient change (MWPC). Known-groups validity and MWPC analyses were also stratified on several pre-defined subgroups. A total of 248 patients were included. Only the QLQ-HCC18 fatigue, nutrition, and index domains demonstrated acceptable internal consistency; acceptable test–retest reliability was found for fatigue, body image, nutrition, pain, sexual interest, and index domains. The QLQ-HCC18 fatigue domain achieved the pre-specified criterion defining acceptable convergent and discriminant validity for 13 of 16 correlations, whereas the index domain achieved the pre-specified criterion for 14 of 16 correlations. Clear differentiation of the QLQ-HCC18 change scores between improvement and maintenance anchor groups were observed for body image, fatigue, pain, and index domains, whereas differentiation between deterioration and maintenance anchor groups were observed for fever and fatigue domains. MWPC point estimates defining improvement for the QLQ-HCC18 fatigue and index domains were −7.18 and −4.07, respectively; MWPC point estimates defining deterioration were 5.34 and 3.16, respectively. The EORTC QLQ-HCC18 fatigue and index domains consistently demonstrated robust psychometric properties, supporting the use of these domains as suitable patient-reported endpoints within a previously treated, unresectable HCC patient population.

PCN192 Psychometric Validation of the EORTC QLQ-HCC18 in Patients with Previously Treated Unresectable Hepatocellular Carcinoma

To evaluate the measurement properties of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (EORTC QLQ-HCC18) within a previously treated, unresectable HCC clinical trial population that was distinct from the published QLQ-HCC18 validation populations.

Patient-reported outcomes (PROs) from the Phase III IMbrave150 trial of atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC).

476 Background: Atezo + bev in pts with unresectable HCC who had not received prior systemic therapy has shown statistically significant and clinically meaningful improvement in OS and PFS per independent review facility-assessed RECIST 1.1 vs sor in the Phase III IMbrave150 study (Cheng ESMO Asia 2019). Here, we report PRO data from this trial to show pt perspectives on the overall clinical benefit of atezo + bev. Methods: Pts were randomized 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg PO BID until loss of clinical benefit or unacceptable toxicity. Pts completed the EORTC QLQ-C30 and EORTC QLQ-HCC18 questionnaires before tx, every 3 wk on tx, and every 3 mo after tx discontinuation or disease progression. A pre-specified secondary endpoint was time to deterioration (TTD; first ≥ 10-point decrease from baseline held for 2 consecutive assessments or 1 assessment followed by death within 3 wk) of pt-reported quality of life (QOL), physical functioning, and role functioning. Pre-specified exploratory analyses included TTD of and proportion of pts with a clinically meaningful change (≥ 10 points from baseline) in key pt-reported symptoms. Results: Questionnaire completion rates were ≥ 92% in both arms from baseline through most of the tx period. Compared with sor, atezo + bev delayed TTD of pt-reported QOL (median TTD, 11.2 vs 3.6 mo; HR, 0.63 [95% CI: 0.46, 0.85]), physical functioning (median TTD, 13.1 vs 4.9 mo; HR, 0.53 [95% CI: 0.39, 0.73]), and role functioning (median TTD, 9.1 vs 3.6 mo; HR, 0.62 [95% CI: 0.46, 0.84]). Atezo + bev also delayed TTD in pt-reported appetite loss, fatigue, pain, and diarrhea vs sor; a lower proportion of pts on atezo + bev experienced clinically meaningful deterioration in each of these symptoms vs sor. Conclusions: High-quality PRO results from IMbrave150 showed large and consistent benefits in key aspects of the pt experience with atezo + bev, further supporting its overall clinical benefit in pts with unresectable HCC who have not received prior systemic therapy. Clinical trial information: NCT03434379.

676PD - Health-related quality of life (HRQoL) impact of pembrolizumab (pembro) versus best supportive care (BSC) in previously systemically treated patients (pts) with advanced hepatocellular carcinoma (HCC): KEYNOTE-240

676PD - Health-related quality of life (HRQoL) impact of pembrolizumab (pembro) versus best supportive care (BSC) in previously systemically treated patients (pts) with advanced hepatocellular carcinoma (HCC): KEYNOTE-240

PGI26 - A Review of Patient-Reported Outcomes in Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic steatohepatitis (NASH) is characterized by fat build up in the liver and results in inflammation and liver cell damage. NASH is rapidly becoming one of the top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Patient-reported outcome (PRO) measures are an important component to assessing disease impact and therapy response in patients with NASH. The objective of this research is to identify commonly used PROs in NASH, evaluate their development, and assess their utility in various types of studies. A literature review using PubMed and a search on clinicaltrials.gov was conducted to identify PROs used in NASH studies. These PROs were evaluated against the FDA’s PRO Guidance criteria with regard to: (1) content validity, particularly patient input in concept elicitation, item generation, and cognitive debriefing; and (2) psychometric testing, particularly construct validity, internal consistency reliability, test-retest reliability, and responsiveness. Each criteria was assessed and given a rating. Finally, an attempt was made to make recommendations on which PROs should be used in different types of studies. Only one NASH-specific PRO publication currently exists: the NASH-CHECK. The NASH-CHECK has only gone through qualitative validation and needs further psychometric analyses. Other PROs used in NASH are generic liver-related measures such as the Chronic Liver Disease Questionnaire, the EORTC QLQ-HCC18 (EORTC Quality of Life Questionnaire - Hepatocellular Carcinoma / Primary Liver Cancer Module), and the LDQOL | Liver Disease Quality of Life Questionnaire. Generic VAS scales have also been used to measure condition- specific symptoms such as itching. Other PRO measures have been appropriately validated but not in specifically in the NASH population. Most PROs used in NASH are borrowed from other diseases or are general PROs and do not address the specific symptoms or concerns of NASH patients. As such, there is need for further NASH-specific PRO development.

Differences in health-related quality of life between European and Asian patients with hepatocellular carcinoma.

The aim of this study is to explore the possible effects of clinical and cultural characteristics of hepatocellular carcinoma on patients' health-related quality of life (HRQoL). Patients with hepatocellular carcinoma from Asian and European countries completed the EORTC QLQ-C30 and the EORTC QLQ-HCC18. Comparisons were made using Student's t-test and Wilcoxon rank-sum test with method of false discovery to correct multiple comparisons. Multiway analysis of variance and model selection were used to assess the effects of clinical characteristics and geographic areas. Two hundred and twenty-seven patients with hepatocellular carcinoma completed questionnaires. After adjusting for demographic and clinical characteristics, Asian patients still had significantly better HRQoL scores in emotional functioning, insomnia, (QLQ-C30) and in sexual interest (QLQ-HCC18). We also found an interaction in physical functioning (QLQ-C30) and fatigue (QLQ-HCC18) between geographic region and marital status, married European had worse HRQoL scores than Asian singles. Both clinical characteristics and geographic areas affected the HRQoL in with hepatocellular carcinoma. Cultural differences and clinical differences in the pattern of disease due to active surveillance of Asian countries may explain the results.

Development and Validation of the Simplified Chinese Version of EORTC QLQ-HCC18 for Patients with Hepatocellular Carcinoma

This study aimed to develop and validate the Simplified Chinese Version of the Quality of Life Questionnaire for Hepatocellular Carcinoma (the QLQ-HCC18). It was developed by the strict translation procedure of EORTC guidelines, and the psychometrics were evaluated on a sample of 114 patients. The internal consistency Cronbach's α were greater than 0.60 for all domains (exception of Jaundice 0.38), and all test–retest reliability coefficients were greater than 0.80. Four out of eight domains had statistically significant changes with effect size standardized response mean (SRM) ranging from 0.31 to 0.73. The Simplified Chinese version of QLQ-HCC18 demonstrates good validity, reliability, and responsiveness.

Important and relevant symptoms including pain concerns in hepatocellular carcinoma (HCC): a patient interview study

We examined the health-related quality of life (HRQOL) and pain experiences of patients with hepatocellular carcinoma (HCC) and assessed content validity of existing patient-reported pain items for patients with HCC. Semi-structured interviews to elicit symptoms, side effects and concerns were conducted with ten patients with HCC. Symptom and side effect importance was ranked on a 0 to 10 scale. Patients completed pain items from the Functional Assessment of Cancer Therapy--Hepatocellular (FACT-Hep) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire--Hepatocellular-18 (EORTC QLQ-HCC18). Mean age was 58 years (range 33-77). Spontaneously reported symptoms included fatigue (n = 5), diarrhea (n = 5), skin toxicities (n = 5), and loss of appetite (n = 4). Upon questioning, nine of ten patients reported experiencing pain over the course of their treatment. Over half of the importance rankings given for pain were 8 or higher on a 0 to 10 scale. Abdomen (n = 7) and lower back (n = 3) were the most common sites of pain. Pain onset varied from 6 months pre-diagnosis to over 2 years post-diagnosis. All patients indicated that FACT-Hep and EORTC items adequately assessed their pain. Results support the content validity of FACT-Hep pain items for patients with HCC. The finding that patients typically did not spontaneously report pain but often ranked it as very important for their HRQOL upon questioning suggests a need for systematic, routine pain and other symptom assessment and management as an integral component of patient care in advanced HCC.